VEGF signaling is required for the assembly but not the maintenance of embryonic blood vessels.

Here we investigated the importance of vascular endothelial growth factor (VEGF) signaling to the de novo formation of embryonic blood vessels, vasculogenesis, as opposed to the maintenance of blood vessels. We found that antagonizing the activity of the VEGF signaling pathway by using soluble VEGF receptor 1 (sFlt1) or VEGF antibodies inhibited vasculogenesis that occurs in embryos and in cultures of 7.5 days postcoitus prevascular mesoderm. Antagonist treatment resulted in the formation of clusters of endothelial cells not normally observed during vasculogenesis. In contrast, when embryos with established vasculatures or cultures of vascularized mesoderm were treated with sFlt1 or VEGF antibodies, no discernible alterations to the preexisting blood vessels were observed. These observations indicate that, although VEGF signaling is required to promote the mesenchymal to epithelial transition by which angioblasts assemble into nascent endothelial tubes, it is not required by endothelial cells to maintain their organization as an endothelium.     

Heritable diseases of the blood vessels.

Four inherited disorders known to effect major arteries will be discussed, including Marfan syndrome (MS), Ehlers-Danlos syndrome (EDS), bicuspid aortic valve (BAV) and nonsyndromic familial aortic dissection. Recent advances in understanding their pathophysiology are presented, and how this knowledge impacts on diagnosis, prevention and treatment is discussed.     

Nonlinear analysis of blood flux in human vessels.

Laser Doppler fluxmetry (LDF) is frequently used in research on microcirculation of blood. Usually LDF time series are analysed by conventional linear methods, mainly Fourier analysis. These methods may not be optimal for the investigation of nonlinear effects of vasomotion, heartbeat or vessels. Nonlinear methods are based on a reconstruction of the system trajectory in an embedding space describing not only the measured time series but the behaviour of the whole system. The fill factor is a tool for displaying the main properties of this attractor in two dimensions and for determining diverse parameters for further analysis. A quantitative characterization of the system is possible by the distribution of correlation dimensions in the embedding space. The singular value decomposition (SVD) can be used to display and characterize individual degrees of freedom. These methods were applied to LDF time series from nine healthy controls and nine patients with Raynaud's phenomenon due to connective tissue disease. The fill factor and the SVD indicate qualitatively that in the controls vasomotion and heartbeat are the main influences on blood flow and act fairly independently of each other. In the patients there was a mixture of strong but irregular degrees of freedom. The mean and the maximal local correlation dimensions were significantly higher in the patient group. Nonlinear analysis of LDF time series provides additional information which cannot be detected using conventional approaches.     

Platelets and blood vessels: the adhesion event.

Circulating blood platelets attach to damaged blood vessels by specific adhesion molecules. In the human arterial circulation, a unique 'shear-dependent' mechanism governs adhesion by a single receptor-ligand (glycoprotein Ib-von Willebrand factor) pair. Here, Gerald Roth reviews recent data that provide insights into the functions of these molecules.     

Intratumoral proliferation of the blood vessels

The growth of vessels in experimental neoplasm occurs within 2-7 days after implantation. Newly formed vessels penetrate into the tumor only from the tissues of the tumor-carrying host. Vessels are formed in the tumor by budding. Proliferation of tumor cells begins only after the contact between them and the developing vascular network has been established. Myofibroblasts play an important role in the development of vessels. The intensity of new vessel formation is more than twice as high as in the wound process. The number of capillaries in developed tumors varies with an average of 30,000 in 1 mm2. Blood supply even within the same tumor is variable both in the form and location of the vessels. With increasing tumor volume intercapillary distances, diameter and length of the capillaries increase while the vascular bed volume, the general and local blood flow decrease. Reparation of the vascular bed in tumors occurs both due to preexisting vessels and by additional formation of new vessels. The muscular layer and innervation are lacking in the newly formed vessels. In the process of growth, compensatory-adaptative reactions directed to improvement of hemodynamics constantly develop in tumor tissues.     

Morphometric evaluation of endometrial blood vessels

Five hundred endometrial specimens were studied to document the changes in blood vessels in various phases of menstrual cycle, menstrual disturbances and in unexplained infertility. Sixty-three cases were taken as control and 437 cases as study group which included cases of dysfunctional uterine bleeding (DUB), endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium. Using light microscopy, the vascular morphology was studied. The blood vessels were concentrated more in basal layer in the proliferative phase and in functional layer in the secretory phase. Cases of complex hyperplasia and pill endometrium had significantly higher vessel concentration. Congestion and dilatation of blood vessels were significantly higher in cases of DUB. The present study showed a positive correlation between endometrial angiogenesis and menstrual disorders. The alteration in blood vessel morphology has significant role in prognosis and in various anti-angiogenic therapies.     

Immunohistochemical differentiation between lymphangiographically verified lymphatic vessels and blood vessels

Summary In order to investigate the antigen profile in human lymphatic vessels when compared with blood vessels, postmortem retrograde lymphangiography was done via the thoracic duct on six patients. Formalin fixed, paraffin embedded tissue was stained immunohistochemically for Factor VIII-Related antigen (F VIII R:Ag), with Ulex Europaeus 1 lectin (UEA-1) and for laminin. The results show that the endothelium of blood vessels and lymphatics at all levels of the lymphatic system react positively following staining for Factor VIII-R:Ag and with UEA-1 lectin. The staining for F VIII R:Ag was generally weaker in the endothelial cells lining lymphatic vessels. Staining for the basement membrane component laminin can be used to distinguish lymphatic capillaries and smaller lymphatic collecting vessels from blood vessels.     

Postnatal persistence of spongy myocardium with embryonic blood supply.

Focal presence of the embryonic pattern of myoarchitecture and of a lacunary blood supply was found in the left ventricular wall of five infant hearts. Four of these hearts showed various malformations; one was a case of cardiac fibroma. The persisting intertrabecular spaces and sinusoids communicated with the ventricular lumen; there appeared to be some communication with the coronary branches. The intertrabecular spaces of the spongy myocardium were lined with a continuous layer of endothelial cells, thus resembling the microscopical appearance of myocardium of adult cold-blooded vertebrates rather than the embryonic phase of myocardial development of warm-blooded animals.